P678: EARLY WARNING RESPONSES IN CML PATIENTS: A REAL-LIFE TURIN EXPERIENCE
Authors: Valentina Giai, Matteo Bisio, Tiziana Rosso, Irene Urbino, Chiara Frairia, Matteo Olivi, Giuseppe Lanzarone, Mattia D’agostino, Eloise Beggiato, Stefano D’ ardia, Ernesta Audisio, Marco Cerrano, Dario Ferrero, Patrizia Pregno, Roberto Freilone
Journal: HemaSphere (2023)

Background: In the last decades, tyrosine kinase inhibitors (TKI) have not only improved biological responses, but also survival and quality of life of chronic myeloid leukemia (CML) patients. In the large registration studies, results are usually exceptional and sometimes not so reproducible in a real-life setting. Aims: Our project aims to analyze the role of “warning” category in a real-life experience. Methods: In our retrospective study, we collected molecular responses and clinical data of CML patients followed at Città della Salute e della Scienza in Turin, Italy. Responses were evaluated according to CML ELN 2020 recommendations (Hochhaus A., Leukemia 2020). Results: One-hundred-sixty-two patients were analyzed: 101 were males (62%), median age was 62 years. Ninety-seven percent of patients was in chronic phase. ELTS score was high in 10.5%, intermediate in 34%, low in 54.3% and missing in 1.2% of patients. Median follow up was 5.5 years. At 3 months, 17% (23/135) of patients showed a warning. Thirteen were receiving Imatinib (IMA), 7 Dasatinib (DAS) and 3 Nilotinib (NIL). All patients except one continued the same treatment. At 6 months, 9 of these patients stayed in the warning category (8 on IMA, 1 on DAS), while 9 reached the failure group (2 on IMA, 4 on DAS, 3 on NIL) and 4 gained the optimal response (2 on IMA, 2 on DAS). Six of the 9 failure patients switched to Ponatinib (PON), 1 to DAS and 2 to NIL. At the 12th month, 5 of the 9 warning patients jumped into the failure category and 4 stayed in the warning group. Six of the 3 months warning patients (6/23, 26,1%) underwent to an allogeneic stem cell transplantation and 5 patients (5/23, 21,7%) died for CML related causes. At 6 months, 24/145 (18%) patients were in the “warning” group. Half of the 6th month warning patients stayed in the warning group even at the 12th month (50%, 15/24). Just 4/24 6th months warning patients changed treatment. The higher warning percentage was detected at 12 months: 39,1% (52/137). 27 were on first line IMA of which 5 changed therapy before the 12 month because of an insufficient response at 6 months; 15 were on first line DAS of which 4 switched therapy before 12 months; 10 were on first line nilotinib (NIL) of which just 1 changed treatment before the 12 months. Half of patients (26/52, 50%) reached optimal response at 24 months, only 2 switched therapy between 12th and 24th month, one for extra hematologic toxicity and the other for warning response. Nine of them were still on first line treatment, even if they were in the warning category already at 3-6 or 12 months (1 on DAS and 8 on IMA). Just 3 patients switched therapy before the 12th month (Fig.1). Global overall survival (OS) in our population was 85,7% at 5 years and 75% at 10 years. Three months warning patients showed a worst OS, compared to the optimal response patients (Fig. 2). No differences in OS were detected among patients treated with different TKI. Summary/Conclusion: In our real-life study, we confirm that warning patients at 6 and 12 months can reach deeper molecular responses at following timepoints even without switching to a second line TKI. OS of warning patients at 6 and 12 months show no significant differences compared to optimal response patients OS. In our registry, all 5 patients that died for CML related causes showed a warning response at 3 months, confirming that early responses can anticipate later responses. Further studies are needed to elucidate role of early “warning” category in a larger setting of CML patients with longer follow up.Keywords: Molecular response, BCR-ABL, Tyrosine kinase inhibitor, Chronic myeloid leukemia